The healthy eye possesses a unique physiological and evolutionary adaptation that modifies the expression of immunity. This physiological adaptation is part of ocular immune privilege. The physiological role of immune privilege is to impart upon the eye immune protection that avoids the destructive side effects of immunogenic inflammation. Immunogenic inflammation associated with hypersensitivity reactions can grossly distort the visual axis resulting in blindness. Within the immune privileged ocular microenvironment, there are active mechanisms of immunoregulation and immunosuppression. This ocular system of immunoregulation and immunosuppression not only suppresses immunogenic inflammation, but also actively manipulates immunity to make the immune response itself immunosuppressive. By understanding the mechanism of ocular immunity, it will be possible to induce an immune response that promotes the elimination of pathogens and tumors without the consequences of immunogenic inflammation, prevent or cure ocular and other autoimmune diseases, and induce immunity that promotes acceptance of corneal, retinal, and other tissue transplants. The objectives of this proposal are to identify, characterize, and establish the role of constitutively produced factors that are immunoregulatory and immunosuppressive in the eye. We hypothesize that the such factors suppress the activation of innate and adaptive immunity associated with inflammation, while enhancing or maintaining expression of the characteristics associated with immune regulation or suppression. We will test this hypothesis by demonstrating that the ocular microenvironment promotes the alternative activation and induction of suppressor macrophages, that the ocular microenvironment promotes the induction of effector regulatory T cells, and that the nervous system makes a significant contribution to ocular immunity.